Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism

Steven D. Freedman, Paola G. Blanco, Munir M. Zaman, Julie C. Shea, Mario Ollero, Isabel K. Hopper, Deborah A. Weed, Andres Gelrud, Meredith M. Regan, Michael Laposata, Juan G. Alvarez, Brian P. O'Sullivan

Research output: Contribution to journalArticle

266 Citations (Scopus)

Abstract

BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.

Original languageEnglish (US)
Pages (from-to)560-569
Number of pages10
JournalNew England Journal of Medicine
Volume350
Issue number6
DOIs
StatePublished - Feb 5 2004
Externally publishedYes

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Cystic Fibrosis
Fatty Acids
Docosahexaenoic Acids
Nose
Cystic Fibrosis Transmembrane Conductance Regulator
Heterozygote
Biopsy
Arachidonic Acid
Knockout Mice
Respiratory Tract Infections
Healthy Volunteers
Asthma
Exocrine Pancreatic Insufficiency
Nasal Mucosa
Regulator Genes
Inflammatory Bowel Diseases
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Freedman, S. D., Blanco, P. G., Zaman, M. M., Shea, J. C., Ollero, M., Hopper, I. K., ... O'Sullivan, B. P. (2004). Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism. New England Journal of Medicine, 350(6), 560-569. https://doi.org/10.1056/NEJMoa021218

Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism. / Freedman, Steven D.; Blanco, Paola G.; Zaman, Munir M.; Shea, Julie C.; Ollero, Mario; Hopper, Isabel K.; Weed, Deborah A.; Gelrud, Andres; Regan, Meredith M.; Laposata, Michael; Alvarez, Juan G.; O'Sullivan, Brian P.

In: New England Journal of Medicine, Vol. 350, No. 6, 05.02.2004, p. 560-569.

Research output: Contribution to journalArticle

Freedman, SD, Blanco, PG, Zaman, MM, Shea, JC, Ollero, M, Hopper, IK, Weed, DA, Gelrud, A, Regan, MM, Laposata, M, Alvarez, JG & O'Sullivan, BP 2004, 'Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism', New England Journal of Medicine, vol. 350, no. 6, pp. 560-569. https://doi.org/10.1056/NEJMoa021218
Freedman SD, Blanco PG, Zaman MM, Shea JC, Ollero M, Hopper IK et al. Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism. New England Journal of Medicine. 2004 Feb 5;350(6):560-569. https://doi.org/10.1056/NEJMoa021218
Freedman, Steven D. ; Blanco, Paola G. ; Zaman, Munir M. ; Shea, Julie C. ; Ollero, Mario ; Hopper, Isabel K. ; Weed, Deborah A. ; Gelrud, Andres ; Regan, Meredith M. ; Laposata, Michael ; Alvarez, Juan G. ; O'Sullivan, Brian P. / Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism. In: New England Journal of Medicine. 2004 ; Vol. 350, No. 6. pp. 560-569.
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abstract = "BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.",
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AU - Freedman, Steven D.

AU - Blanco, Paola G.

AU - Zaman, Munir M.

AU - Shea, Julie C.

AU - Ollero, Mario

AU - Hopper, Isabel K.

AU - Weed, Deborah A.

AU - Gelrud, Andres

AU - Regan, Meredith M.

AU - Laposata, Michael

AU - Alvarez, Juan G.

AU - O'Sullivan, Brian P.

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N2 - BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.

AB - BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.

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